A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Ganoderma lucidum is a mushroom widely used for its edible and medicinal properties. Primary bioactive constituents of G. lucidum are ganoderic triterpenoids (GTs), which exhibit important pharmacological activity. Abscisic acid (ABA), a plant hormone, is associated with plant growth, development, and stress responses. ABA can also affect the growth, metabolism, and physiological activities of different fungi and participates in the regulation of the tetracyclic triterpenes of some plants. Our findings indicated that ABA treatment promoted GT accumulation by regulating the gene expression levels (squalene synthase (sqs), 3-hydroxy-3-methylglutaryl-CoA reductase (hmgr), and lanosterol synthase (ls)), and also activated cytosolic Ca²⁺ channels. Furthermore, under ABA mediation, exogenous Ca²⁺ donors and inhibitors directly affected the cytosolic Ca²⁺ concentration and related gene expression in Ca²⁺ signaling. Our study also revealed that ABA-mediated cytosolic Ca²⁺ played a crucial regulatory role in GT biosynthesis, accompanied by antioxidant defense modulation with increasing superoxide dismutase (SOD) activity and ascorbate peroxidase (APX) activity, and the resistance ability of O₂^•- and glutathione (GSH) contents.
Reishi/metabolism* ; Triterpenes/metabolism* ; Abscisic Acid/metabolism* ; Antioxidants/metabolism*

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62⁺ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62⁺ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

Objective:To investigate the intention to obtain disease related information and its influencing factors among the elderly at their end-of-life stage.Methods:A cross-sectional survey was conducted among 414 elderly people aged ≥60 in 7 long-term residential care facilities and 15 communities in the central urban area of Fuzhou using the late-life care preference questionnaire from October 2016 to June 2017. Univariate analysis, multiple linear regression analysis and ordered multi-classification logistic regression analysis were used to identify information preference of the disease-related information and influencing factors among the elderly.Results:The level of disease-related information needs of the elderly was scored (17.1±4.9); 48.8% (202/414) preferred detailed or maximum information; 30.7% (127/414) wanted selective and partial information; 20.5% (85/414) did not want to know any information. Multiple linear regression analysis showed that age, education, and whether or not they had received or seen other life-sustaining treatments were the main factors affecting the level of disease-related information needs (standardized regression coefficients were -0.141, 0.116, 0.115, all P<0.05); ordered multi-classification logistic regression analysis showed that age (compared with 60-69 years old, 70-79 years old: OR=0.544, 95% CI: 0.310-0.957; 80-89 years old: OR=0.526, 95% CI: 0.289-0.956), education level (compared with primary school and below, college or above: OR=2.166, 95% CI: 1.093-4.290), main sources of living expenses (compared with other allowance, family support: OR=7.303, 95% CI: 1.157-46.108, pension: OR=9.288, 95% CI: 1.502-57.415; provident fund scheme/saving: OR=15.676, 95% CI: 2.122-115.793), whether or not they had received or seen other life-sustaining treatments (compared with yes, OR=1.985, 95% CI: 1.150-3.425) were the main factors affecting the level of disease-related information needs. Conclusions:Most of the elderly prefer to know disease-related information. Age, educational level, main sources of living expenses and whether or not they had received or seen other life-sustaining treatments are the main influencing factors.

A new electrochemical sensor for organophosphate pesticide(methyl-paraoxon)detection based on bifunctional cerium oxide(CeO2)nanozyme is here reported for the first time.Methyl-paraoxon was degraded into p-nitrophenol by using CeO2 with phosphatase mimicking activity.The CeO2 nanozyme-modified electrode was then synthesized to detect p-nitrophenol.Cyclic voltammetry was applied to investigate the electrochemical behavior of the modified electrode,which indicates that the signal enhancement effect may attribute to the coating of CeO2 nanozyme.The current research also studied and discussed the main parameters affecting the analytical signal,including accumulation potential,accumulation time,and pH.Under the optimum conditions,the present method provided a wider linear range from 0.1 to 100 μmol/L for methyl-paraoxon with a detection limit of 0.06 μmol/L.To validate the proof of concept,the electrochemical sensor was then successfully applied for the determination of methyl-paraoxon in three herb samples,i.e.,Coix lacryma-jobi,Adenophora stricta and Semen nelum-binis.Our findings may provide new insights into the application of bifunctional nanozyme in electro-chemical detection of organophosphorus pesticide.

Objective:To investigate the clinical effect of fingertip reconstruction using the toenail osteocutaneous flap without vascular anastomosis.Methods:From January 2015 to October 2020, the clinical data of patients with fingertip injuries were analyzed retrospectively, which were treated with the toenail osteocutaneous flap without vascular anastomosis in Chang’an Xin’an Hospital. The donor site was closed primarily or covered by a local flap. The appearance and function of the patients’ fingers were followed up. All cases were evaluated by the standard of thumb finger reconstruction function evaluation of the Chinese Medical Association of Hand Surgery. Appearance and function of nail bed after reconstruction was evaluated from four aspects.Results:A total of 11 cases (12 fingers) were enrolled, including eight males and three females. The average age was 35.6 years (range, 17-50 years). The etiologies included crush-related injury, cutting injury, mangled injury, and chemical corrosion injury. The injuries were found in thumb, index finger, middle finger, ring finger, or combined with multiple fingers. All fingertip defects were located distal to the nail root, including the defects distal to lunula in four cases, the defects distal to middle of the nail in five fingers , and the defects distal to 1/3 of the nail in three cases. Elective surgery was performed in 7 cases and emergency surgery in 4 cases. The defects ranged from 0.2 cm/0.5 cm/0.5 cm to 0.6 cm/0.8 cm/1.0 cm (phalanx/nail/finger pulp). The size of the toenail osteocutaneous flap ranged from 0.2 cm/0.5 cm/0.7 cm to 0.6 cm/0.8 cm/1.0 cm (phalanx/nail/flap). The defects length of the finger pulp were less than 1.0 cm. All reconstructed fingers survived, and the follow-up was 6-30 months (average, 12.5 months). The appearances of the reconstructed fingers were pulmp and ruddy, and the nails were flat. There was no dysfunction in the donor site. The average healing time of bone was 2.1 months (range, 1.5-3.0 months). According to the evaluation of index function, seven cases were excellent, four cases were good. The appearance and function of the nail bed were excellent in six fingers, good in five fingers, and poor in one finger.Conclusion:It is a simple and effective way to reconstruct the fingertip using the toenail osteocutaneous flap without vascular anastomosis.

Objective:To investigate the clinical effect of fingertip reconstruction using the toenail osteocutaneous flap without vascular anastomosis.Methods:From January 2015 to October 2020, the clinical data of patients with fingertip injuries were analyzed retrospectively, which were treated with the toenail osteocutaneous flap without vascular anastomosis in Chang’an Xin’an Hospital. The donor site was closed primarily or covered by a local flap. The appearance and function of the patients’ fingers were followed up. All cases were evaluated by the standard of thumb finger reconstruction function evaluation of the Chinese Medical Association of Hand Surgery. Appearance and function of nail bed after reconstruction was evaluated from four aspects.Results:A total of 11 cases (12 fingers) were enrolled, including eight males and three females. The average age was 35.6 years (range, 17-50 years). The etiologies included crush-related injury, cutting injury, mangled injury, and chemical corrosion injury. The injuries were found in thumb, index finger, middle finger, ring finger, or combined with multiple fingers. All fingertip defects were located distal to the nail root, including the defects distal to lunula in four cases, the defects distal to middle of the nail in five fingers , and the defects distal to 1/3 of the nail in three cases. Elective surgery was performed in 7 cases and emergency surgery in 4 cases. The defects ranged from 0.2 cm/0.5 cm/0.5 cm to 0.6 cm/0.8 cm/1.0 cm (phalanx/nail/finger pulp). The size of the toenail osteocutaneous flap ranged from 0.2 cm/0.5 cm/0.7 cm to 0.6 cm/0.8 cm/1.0 cm (phalanx/nail/flap). The defects length of the finger pulp were less than 1.0 cm. All reconstructed fingers survived, and the follow-up was 6-30 months (average, 12.5 months). The appearances of the reconstructed fingers were pulmp and ruddy, and the nails were flat. There was no dysfunction in the donor site. The average healing time of bone was 2.1 months (range, 1.5-3.0 months). According to the evaluation of index function, seven cases were excellent, four cases were good. The appearance and function of the nail bed were excellent in six fingers, good in five fingers, and poor in one finger.Conclusion:It is a simple and effective way to reconstruct the fingertip using the toenail osteocutaneous flap without vascular anastomosis.

Objective:To investigate the clinical effect of free anterior tibial artery proximal periosteal perforator bone-skin flap for repairing phased thumb defect.Methods:Eight patients of phased defect of thumb were repaired from March, 2013 to January, 2019 utilizing proximal tibial artery periosteal perforator bone and skin flap. Of which, 2 cases suffered defects at interphalangeal joint of thumb, 3 in proximal phalanx, and 3 at thenar muscle and metacarpale. There were 4 cases with tendon defect, 6 cases with other finger injuries.The areas of soft tissue defect was 4.5 cm×2.5 cm to 7.2 cm×4.0 cm, and the length of metacarpale bone defect was 1.2 to 2.5 cm. The flap size ranged from 5.0 cm×3.0 cm to 7.5 cm×4.5 cm, and the bone flap size was 1.2 cm×1.0 cm×0.8 cm to 2.5 cm×1.0 cm×1.0 cm. Six cases received direct suture or local skin metastasis in anterior tibial region and 2 cases with skin grafting. All patients were followed-up by clinic visits, telephone or WeChat reviews, and home visits.Results:All the flaps survived after surgery. A 6 to 24 months followed-up showed that the flaps were normal in colour with good texture and moderate thickness. TPD of the flaps ranged from 7 to 10 mm. The donor site of the shank had good appearance and were in normal function, and the walking were not affected. Healing time of transplanted bone flaps ranged from 2.0 to 4.0 months, with an average of 2.6 months. According to the Evaluation Criteria of Upper Limb Function of the Hand Surgery Society of Chinese Medical Association, the results were excellent in 7 thumbs and good in 1 thumb. According to Michigan Hand Function Evaluation Criteria, 8 thumbs scored 81.3 to 91.8 points, with an average of 83.6 points.Conclusion:The reconstruction of phased defect of thumb with proximal tibial artery periosteal perforator bone-skin flap can restore the appearance and function of thumb to the greatest extent, and the affect to donor site is minimum. It is an effective surgical method for repairing phased defect of thumb.

OBJECTIVES: To explore and analyze the epidemic features of coronavirus disease 2019 (COVID-19) in Hunan Province from January 21, 2020 to March 14, 2020, as well as to investigate the COVID-19 epidemics in each city of Hunan Province. METHODS: The epidemic data was obtained from the official website of Hunan Province's Health Commission. The data of each city of Hunan Province was analyzed separately. Spatial distribution of cumulative confirmed COVID-19 patients and the cumulative occurrence rate was drawn by ArcGIS software for each city in Hunan Province. Some regional indexes were also compared with that in the whole country. RESULTS: The first patient was diagnosed in January 21, sustained patient growth reached its plateau in around February 17. Up to March 14, the cumulative confirmed COVID-19 patients stopped at 1 018. The cumulative occurrence rate of COVID-19 patients was 0.48 per 0.1 million person. The number of cumulative severe patients was 150 and the number of cumulative dead patients was 4. The mortality rate (0.39%) and the cure rate (99.6%) in Hunan Province was significantly lower and higher respectively than the corresponding average rate in the whole country (0.90% and 96.2%, Hubei excluded). The first 3 cities in numbers of the confirmed patients were Changsha, Yueyang, and Shaoyang. While sorted by the cumulative occurrence rate, the first 3 cities in incidence were Changsha, Yueyang, and Zhuzhou. CONCLUSIONS The epidemic of COVID-19 spread out smoothly in Hunan Province. The cities in Hunan Province implement anti-disease strategies based on specific situations on their own and keep the epidemic in the range of controllable.
Betacoronavirus ; China ; epidemiology ; Cities ; epidemiology ; Coronavirus Infections ; epidemiology ; mortality ; Humans ; Pandemics ; Pneumonia, Viral ; epidemiology ; mortality